Synthesis of Biologically Active Small Molecules: Different Approaches to Drug Design

In the past years, genome biology had disclosed an ever-growing kind of biological targets that emerged as ideal points for therapeutic intervention. Nevertheless, the number of new chemical entities (NCEs) translated into effective therapies employed in the clinic, still not observed. Innovative strategies in drug discovery combined with different approaches to drug design should be searched for bridge this gap. In this context organic synthetic chemistry had to provide for effective strategies to achieve biologically active small molecules to consider not only as potentially drug candidates, but also as chemical tools to dissect biological systems. In this scenario, during my PhD, inspired by the Biology-oriented Synthesis approach, a small library of hybrid molecules endowed with privileged scaffolds, able to block cell cycle and to induce apoptosis and cell differentiation, merged with natural-like cores were synthesized. A synthetic platform which joined a Domino Knoevenagel-Diels Alder reaction with a Suzuki coupling was performed in order to reach the hybrid compounds. These molecules can represent either antitumor lead candidates, or valuable chemical tools to study molecular pathways in cancer cells. The biological profile expressed by some of these derivatives showed a well defined antiproliferative activity on leukemia Bcr-Abl expressing K562 cell lines. A parallel project regarded the rational design and synthesis of minimally structurally hERG blockers with the purpose of enhancing the SAR studies of a previously synthesized collection. A Target-Oriented Synthesis approach was applied. Combining conventional and microwave heating, the desired final compounds were achieved in good yields and reaction rates. The preliminary biological results of the compounds, showed a potent blocking activity. The obtained small set of hERG blockers, was able to gain more insight the minimal structural requirements for hERG liability, which is mandatory to investigate in order to reduce the risk of potential side effects of new drug candidates.

ALMASat-1, ALMASat-EO and beyond: evolution of structural concepts and technologies towards multifunctional structures for microsatellites

Multifunctional Structures (MFS) represent one of the most promising disruptive technologies in the space industry. The possibility to merge spacecraft primary and secondary structures as well as attitude control, power management and onboard computing functions is expected to allow for mass, volume and integration effort savings. Additionally, this will bring the modular construction of spacecraft to a whole new level, by making the development and integration of spacecraft modules, or building blocks, leaner, reducing lead times from commissioning to launch from the current 3-6 years down to the order of 10 months, as foreseen by the latest Operationally Responsive Space (ORS) initiatives. Several basic functionalities have been integrated and tested in specimens of various natures over the last two decades. However, a more integrated, system-level approach was yet to be developed. The activity reported in this thesis was focused on the system-level approach to multifunctional structures for spacecraft, namely in the context of nano- and micro-satellites. This thesis documents the work undertaken in the context of the MFS program promoted by the European Space Agency under the Technology Readiness Program (TRP): a feasibility study, including specimens manufacturing and testing. The work sequence covered a state of the art review, with particular attention to traditional modular architectures implemented in ALMASat-1 and ALMASat-EO satellites, and requirements definition, followed by the development of a modular multi-purpose nano-spacecraft concept, and finally by the design, integration and testing of integrated MFS specimens. The approach for the integration of several critical functionalities into nano-spacecraft modules was validated and the overall performance of the system was verified through relevant functional and environmental testing at University of Bologna and University of Southampton laboratories.

Structural verification of the ESEO spacecraft: from launch loads analysis to composite panels verification

The present thesis work was performed in the frame of ESEO (European Student Earth Orbiter) project. The activities that are described in this document were carried out in the Microsatellites and Space Micro systems Lab led by Professor Paolo Tortora and in ALMASpace company facilities. The thesis deals with ESEO structural analysis, at system and unit level, and verification: after determining the design limit loads to be applied to the spacecraft as an envelope of different launchers load profiles, a finite element structural analysis was performed on the model of the satellite in order to ensure the capability to withstand the loads encountered during the launch; all the analyses were performed according to ESA standards and using the software MSC NASTRAN SIMXPERT. Amplification factors were derived and used to determine loads to be considered at unit level. In particular structural analyses were carried out on the GPS unit, the payload developed for ESEO by students of University of Bologna and results were used in the preparation of GPS payload design definition file. As for the verification phase a study on the panels and inserts to be used in the spacecraft was performed: different designs were created exploiting methods to optimize weight and mechanical behavior. The configurations have been analyzed and results compared to select the final design.

Crystal structure of the Leishmania major phosphodiesterase LmjPDEB1 and insight into the design of the parasite-selective inhibitors

Human leishmaniasis is a major public health problem in many countries, but chemotherapy is in an unsatisfactory state. Leishmania major phosphodiesterases (LmjPDEs) have been shown to play important roles in cell proliferation and apoptosis of the parasite. Thus LmjPDE inhibitors may potentially represent a novel class of drugs for the treatment of leishmaniasis. Reported here are the kinetic characterization of the LmjPDEB1 catalytic domain and its crystal structure as a complex with 3-isobutyl-1-methylxanthine (IBMX) at 1.55 A resolution. The structure of LmjPDEB1 is similar to that of human PDEs. IBMX stacks against the conserved phenylalanine and forms a hydrogen bond with the invariant glutamine, in a pattern common to most inhibitors bound to human PDEs. However, an extensive structural comparison reveals subtle, but significant differences between the active sites of LmjPDEB1 and human PDEs. In addition, a pocket next to the inhibitor binding site is found to be unique to LmjPDEB1. This pocket is isolated by two gating residues in human PDE families, but constitutes a natural expansion of the inhibitor binding pocket in LmjPDEB1. The structure particularity might be useful for the development of parasite-selective inhibitors for the treatment of leishmaniasis.

Vibro-acoustical analysis and design of a multiple-layer constrained viscoelastic damping structure

The goal of this research is to provide a framework for vibro-acoustical analysis and design of a multiple-layer constrained damping structure. The existing research on damping and viscoelastic damping mechanism is limited to the following four mainstream approaches: modeling techniques of damping treatments/materials; control through the electrical-mechanical effect using the piezoelectric layer; optimization by adjusting the parameters of the structure to meet the design requirements; and identification of the damping material’s properties through the response of the structure. This research proposes a systematic design methodology for the multiple-layer constrained damping beam giving consideration to vibro-acoustics. A modeling technique to study the vibro-acoustics of multiple-layered viscoelastic laminated beams using the Biot damping model is presented using a hybrid numerical model. The boundary element method (BEM) is used to model the acoustical cavity whereas the Finite Element Method (FEM) is the basis for vibration analysis of the multiple-layered beam structure. Through the proposed procedure, the analysis can easily be extended to other complex geometry with arbitrary boundary conditions. The nonlinear behavior of viscoelastic damping materials is represented by the Biot damping model taking into account the effects of frequency, temperature and different damping materials for individual layers. A curve-fitting procedure used to obtain the Biot constants for different damping materials for each temperature is explained. The results from structural vibration analysis for selected beams agree with published closed-form results and results for the radiated noise for a sample beam structure obtained using a commercial BEM software is compared with the acoustical results of the same beam with using the Biot damping model. The extension of the Biot damping model is demonstrated to study MDOF (Multiple Degrees of Freedom) dynamics equations of a discrete system in order to introduce different types of viscoelastic damping materials. The mechanical properties of viscoelastic damping materials such as shear modulus and loss factor change with respect to different ambient temperatures and frequencies. The application of multiple-layer treatment increases the damping characteristic of the structure significantly and thus helps to attenuate the vibration and noise for a broad range of frequency and temperature. The main contributions of this dissertation include the following three major tasks: 1) Study of the viscoelastic damping mechanism and the dynamics equation of a multilayer damped system incorporating the Biot damping model. 2) Building the Finite Element Method (FEM) model of the multiple-layer constrained viscoelastic damping beam and conducting the vibration analysis. 3) Extending the vibration problem to the Boundary Element Method (BEM) based acoustical problem and comparing the results with commercial simulation software.

Corrugated wood composite panels for structural decking

High flexural strength and stiffness can be achieved by forming a thin panel into a wave shape perpendicular to the bending direction. The use of corrugated shapes to gain flexural strength and stiffness is common in metal and reinforced plastic products. However, there is no commercial production of corrugated wood composite panels. This research focuses on the application of corrugated shapes to wood strand composite panels. Beam theory, classical plate theory and finite element models were used to analyze the bending behavior of corrugated panels. The most promising shallow corrugated panel configuration was identified based on structural performance and compatibility with construction practices. The corrugation profile selected has a wavelength equal to 8”, a channel depth equal to ¾”, a sidewall angle equal to 45 degrees and a panel thickness equal to 3/8”. 16”x16” panels were produced using random mats and 3-layer aligned mats with surface flakes parallel to the channels. Strong axis and weak axis bending tests were conducted. The test results indicate that flake orientation has little effect on the strong axis bending stiffness. The 3/8” thick random mat corrugated panels exhibit bending stiffness (400,000 lbs-in2/ft) and bending strength (3,000 in-lbs/ft) higher than 23/32” or 3/4” thick APA Rated Sturd-I-Floor with a 24” o.c. span rating. Shear and bearing test results show that the corrugated panel can withstand more than 50 psf of uniform load at 48” joist spacings. Molding trials on 16”x16” panels provided data for full size panel production. Full size 4’x8’ shallow corrugated panels were produced with only minor changes to the current oriented strandboard manufacturing process. Panel testing was done to simulate floor loading during construction, without a top underlayment layer, and during occupancy, with an underlayment over the panel to form a composite deck. Flexural tests were performed in single-span and two-span bending with line loads applied at mid-span. The average strong axis bending stiffness and bending strength of the full size corrugated panels (without the underlayment) were over 400,000 lbs-in2/ft and 3,000 in-lbs/ft, respectively. The composite deck system, which consisted of an OSB sheathing (15/32” thick) nailed-glued (using 3d ringshank nails and AFG-01 subfloor adhesive) to the corrugated subfloor achieved about 60% of the full composite stiffness resulting in about 3 times the bending stiffness of the corrugated subfloor (1,250,000 lbs-in2/ft). Based on the LRFD design criteria, the corrugated composite floor system can carry 40 psf of unfactored uniform loads, limited by the L/480 deflection limit state, at 48” joist spacings. Four 10-ft long composite T-beam specimens were built and tested for the composite action and the load sharing between a 24” wide corrugated deck system and the supporting I-joist. The average bending stiffness of the composite T-beam was 1.6 times higher than the bending stiffness of the I-joist. A 8-ft x 12-ft mock up floor was built to evaluate construction procedures. The assembly of the composite floor system is relatively simple. The corrugated composite floor system might be able to offset the cheaper labor costs of the single-layer Sturd-IFloor through the material savings. However, no conclusive result can be drawn, in terms of the construction costs, at this point without an in depth cost analysis of the two systems. The shallow corrugated composite floor system might be a potential alternative to the Sturd-I-Floor in the near future because of the excellent flexural stiffness provided.

Testing Wisconsin asphalt mixtures for the 2002 AASHTO mechanistic design procedure

There has been a continuous evolutionary process in asphalt pavement design. In the beginning it was crude and based on past experience. Through research, empirical methods were developed based on materials response to specific loading at the AASHO Road Test. Today, pavement design has progressed to a mechanistic-empirical method. This methodology takes into account the mechanical properties of the individual layers and uses empirical relationships to relate them to performance. The mechanical tests that are used as part of this methodology include dynamic modulus and flow number, which have been shown to correlate with field pavement performance. This thesis was based on a portion of a research project being conducted at Michigan Technological University (MTU) for the Wisconsin Department of Transportation (WisDOT). The global scope of this project dealt with the development of a library of values as they pertain to the mechanical properties of the asphalt pavement mixtures paved in Wisconsin. Additionally, a comparison with the current associated pavement design to that of the new AASHTO Design Guide was conducted. This thesis describes the development of the current pavement design methodology as well as the associated tests as part of a literature review. This report also details the materials that were sampled from field operations around the state of Wisconsin and their testing preparation and procedures. Testing was conducted on available round robin and three Wisconsin mixtures and the main results of the research were: The test history of the Superpave SPT (fatigue and permanent deformation dynamic modulus) does not affect the mean response for both dynamic modulus and flow number, but does increase the variability in the test results of the flow number. The method of specimen preparation, compacting to test geometry versus sawing/coring to test geometry, does not statistically appear to affect the intermediate and high temperature dynamic modulus and flow number test results. The 2002 AASHTO Design Guide simulations support the findings of the statistical analyses that the method of specimen preparation did not impact the performance of the HMA as a structural layer as predicted by the Design Guide software. The methodologies for determining the temperature-viscosity relationship as stipulated by Witczak are sensitive to the viscosity test temperatures employed. The increase in asphalt binder content by 0.3% was found to actually increase the dynamic modulus at the intermediate and high test temperature as well as flow number. This result was based the testing that was conducted and was contradictory to previous research and the hypothesis that was put forth for this thesis. This result should be used with caution and requires further review. Based on the limited results presented herein, the asphalt binder grade appears to have a greater impact on performance in the Superpave SPT than aggregate angularity. Dynamic modulus and flow number was shown to increase with traffic level (requiring an increase in aggregate angularity) and with a decrease in air voids and confirm the hypotheses regarding these two factors. Accumulated micro-strain at flow number as opposed to the use of flow number appeared to be a promising measure for comparing the quality of specimens within a specific mixture. At the current time the Design Guide and its associate software needs to be further improved prior to implementation by owner/agencies.

Control design and genetic algorithm optimization for electrostatic MEMS

This dissertation discusses structural-electrostatic modeling techniques, genetic algorithm based optimization and control design for electrostatic micro devices. First, an alternative modeling technique, the interpolated force model, for electrostatic micro devices is discussed. The method provides improved computational efficiency relative to a benchmark model, as well as improved accuracy for irregular electrode configurations relative to a common approximate model, the parallel plate approximation model. For the configuration most similar to two parallel plates, expected to be the best case scenario for the approximate model, both the parallel plate approximation model and the interpolated force model maintained less than 2.2% error in static deflection compared to the benchmark model. For the configuration expected to be the worst case scenario for the parallel plate approximation model, the interpolated force model maintained less than 2.9% error in static deflection while the parallel plate approximation model is incapable of handling the configuration. Second, genetic algorithm based optimization is shown to improve the design of an electrostatic micro sensor. The design space is enlarged from published design spaces to include the configuration of both sensing and actuation electrodes, material distribution, actuation voltage and other geometric dimensions. For a small population, the design was improved by approximately a factor of 6 over 15 generations to a fitness value of 3.2 fF. For a larger population seeded with the best configurations of the previous optimization, the design was improved by another 7% in 5 generations to a fitness value of 3.0 fF. Third, a learning control algorithm is presented that reduces the closing time of a radiofrequency microelectromechanical systems switch by minimizing bounce while maintaining robustness to fabrication variability. Electrostatic actuation of the plate causes pull-in with high impact velocities, which are difficult to control due to parameter variations from part to part. A single degree-of-freedom model was utilized to design a learning control algorithm that shapes the actuation voltage based on the open/closed state of the switch. Experiments on 3 test switches show that after 5-10 iterations, the learning algorithm lands the switch with an impact velocity not exceeding 0.2 m/s, eliminating bounce.

Inductive-Capacitive Resonant Circuit Sensors for Structural Health and Environmental Monitoring

Inductive-capacitive (LC) resonant circuit sensors are low-cost, wireless, durable, simple to fabricate and battery-less. Consequently, they are well suited to sensing applications in harsh environments or in situations where large numbers of sensors are needed. They are also advantageous in applications where access to the sensor is limited or impossible or when sensors are needed on a disposable basis. Due to their many advantages, LC sensors have been used for sensing a variety of parameters including humidity, temperature, chemical concentrations, pH, stress/pressure, strain, food quality and even biological growth. However, current versions of the LC sensor technology are limited to sensing only one parameter. The purpose of this work is to develop new types of LC sensor systems that are simpler to fabricate (hence lower cost) or capable of monitoring multiple parameters simultaneously. One design presented in this work, referred to as the multi-element LC sensor, is able to measure multiple parameters simultaneously using a second capacitive element. Compared to conventional LC sensors, this design can sense multiple parameters with a higher detection range than two independent sensors while maintaining the same overall sensor footprint. In addition, the two-element sensor does not suffer from interference issues normally encountered while implementing two LC sensors in close proximity. Another design, the single-spiral inductive-capacitive sensor, utilizes the parasitic capacitance of a coil or spring structure to form a single layer LC resonant circuit. Unlike conventional LC sensors, this design is truly planar, thus simplifying its fabrication process and reducing sensor cost. Due to the simplicity of this sensor layout it will be easier and more cost-effective for embedding in common building or packaging materials during manufacturing processes, thereby adding functionality to current products (such as drywall sheets) while having a minor impact on overall unit cost. These modifications to the LC sensor design significantly improve the functionality and commercial feasibility of this technology, especially for applications where a large array of sensors or multiple sensing parameters are required.

STRUCTURAL CONTROL OF A SMALL-SCALE TEST-BED SHAKER STRUCTURE USING A SPONGE-TYPE MAGNETO-RHEOLOGICAL FLUID DAMPER

Semi-active damping devices have been shown to be effective in mitigating unwanted vibrations in civil structures. These devices impart force indirectly through real-time alterations to structural properties. Simulating the complex behavior of these devices for laboratory-scale experiments is a major challenge. Commercial devices for seismic applications typically operate in the 2-10 kN range; this force is too high for small-scale testing applications where requirements typically range from 0-10 N. Several challenges must be overcome to produce damping forces at this level. In this study, a small-scale magneto-rheological (MR) damper utilizing a fluid absorbent metal foam matrix is developed and tested to accomplish this goal. This matrix allows magneto-rheological (MR) fluid to be extracted upon magnetic excitation in order to produce MR-fluid shear stresses and viscosity effects between an electromagnetic piston, the foam, and the damper housing. Dampers for uniaxial seismic excitation are traditionally positioned in the horizontal orientation allowing MR-fluid to gather in the lower part of the damper housing when partially filled. Thus, the absorbent matrix is placed in the bottom of the housing relieving the need to fill the entire device with MR-fluid, a practice that requires seals that add significant unwanted friction to the desired low-force device. The damper, once constructed, can be used in feedback control applications to reduce seismic vibrations and to test structural control algorithms and wireless command devices. To validate this device, a parametric study was performed utilizing force and acceleration measurements to characterize damper performance and controllability for this actuator. A discussion of the results is presented to demonstrate the attainment of the damper design objectives.

MODEL UPDATING AND STRUCTURAL HEALTH MONITORING OF HORIZONTAL AXIS WIND TURBINES VIA ADVANCED SPINNING FINITE ELEMENTS AND STOCHASTIC SUBSPACE IDENTIFICATION METHODS

Wind energy has been one of the most growing sectors of the nation’s renewable energy portfolio for the past decade, and the same tendency is being projected for the upcoming years given the aggressive governmental policies for the reduction of fossil fuel dependency. Great technological expectation and outstanding commercial penetration has shown the so called Horizontal Axis Wind Turbines (HAWT) technologies. Given its great acceptance, size evolution of wind turbines over time has increased exponentially. However, safety and economical concerns have emerged as a result of the newly design tendencies for massive scale wind turbine structures presenting high slenderness ratios and complex shapes, typically located in remote areas (e.g. offshore wind farms). In this regard, safety operation requires not only having first-hand information regarding actual structural dynamic conditions under aerodynamic action, but also a deep understanding of the environmental factors in which these multibody rotating structures operate. Given the cyclo-stochastic patterns of the wind loading exerting pressure on a HAWT, a probabilistic framework is appropriate to characterize the risk of failure in terms of resistance and serviceability conditions, at any given time. Furthermore, sources of uncertainty such as material imperfections, buffeting and flutter, aeroelastic damping, gyroscopic effects, turbulence, among others, have pleaded for the use of a more sophisticated mathematical framework that could properly handle all these sources of indetermination. The attainable modeling complexity that arises as a result of these characterizations demands a data-driven experimental validation methodology to calibrate and corroborate the model. For this aim, System Identification (SI) techniques offer a spectrum of well-established numerical methods appropriated for stationary, deterministic, and data-driven numerical schemes, capable of predicting actual dynamic states (eigenrealizations) of traditional time-invariant dynamic systems. As a consequence, it is proposed a modified data-driven SI metric based on the so called Subspace Realization Theory, now adapted for stochastic non-stationary and timevarying systems, as is the case of HAWT’s complex aerodynamics. Simultaneously, this investigation explores the characterization of the turbine loading and response envelopes for critical failure modes of the structural components the wind turbine is made of. In the long run, both aerodynamic framework (theoretical model) and system identification (experimental model) will be merged in a numerical engine formulated as a search algorithm for model updating, also known as Adaptive Simulated Annealing (ASA) process. This iterative engine is based on a set of function minimizations computed by a metric called Modal Assurance Criterion (MAC). In summary, the Thesis is composed of four major parts: (1) development of an analytical aerodynamic framework that predicts interacted wind-structure stochastic loads on wind turbine components; (2) development of a novel tapered-swept-corved Spinning Finite Element (SFE) that includes dampedgyroscopic effects and axial-flexural-torsional coupling; (3) a novel data-driven structural health monitoring (SHM) algorithm via stochastic subspace identification methods; and (4) a numerical search (optimization) engine based on ASA and MAC capable of updating the SFE aerodynamic model.

Conformationally homogeneous heterocyclic pseudotetrapeptides as three-dimensional scaffolds for rational drug design: receptor-selective somatostatin analogues

A would-be amide: A 1,4-disubstituted 1,2,3-triazole was used as a surrogate for a trans amide bond to create a library of 16 diastereomeric pseudotetrapeptides as beta-turn mimetics. High-resolution structural analysis indicated that these scaffolds adopt distinct, rigid, conformationally homogeneous beta-turn-like structures (see example), some of which bind somatostatin receptor subtypes selectively, and some of which show broad-spectrum activity.

Making epothilones fluoresce: design, synthesis, and biological characterization of a fluorescent N12-aza-epothilone (azathilone)

A green fluorescent 12-aza-epothilone (azathilone) derivative has been prepared through the attachment of the 4-nitro-2,1,3-benzoxadiazole (NBD) fluorophore to the 12-nitrogen atom of the azamacrolide core structure. While less potent than natural epothilones or different N12-acylated azathilone derivatives, NBD-azathilone (3) promotes tubulin assembly, inhibits cancer cell proliferation in vitro and arrests the cell cycle at the G2/M transition. Most significantly, the binding of 3 to cellular microtubules (MTs) could be directly visualized by confocal fluorescence microscopy. Based on competition binding experiments with laulimalide-stabilized MTs in vitro, the N12-Boc substituted azathilone 1, Epo A, and NBD-azathilone (3) all interact with the same tubulin-binding site. Computational studies provided a structural model of the complexes between beta-tubulin and 1 or 3, respectively, in which the NBD moiety of 3 or the BOC moiety of 1 directly and specifically contribute to MT binding. Collectively, these data demonstrate that the cellular effects of 3 and, by inference, also of other azathilones are the result of their interactions with the cellular MT network.

Purchasing Organization and Design: A Literature Review

This paper presents the results of a comprehensive literature review of the organization of purchasing covering the period from 1967 to 2009. The review provides a structured overview of prior research topics and findings and identifies gaps in the existing literature that may be addressed in future research. The intention of the review is to a) synthesize prior research, b) provide researchers with a structural framework on which future research on the organization of purchasing may be oriented, and c) suggest promising areas for future research.

Design and evaluation of the parent education component of a comprehensive violence prevention project in middle schools

Low parental monitoring is related to youth risk behaviors such as delinquency and aggression. The purpose of this dissertation was to describe the development and evaluation of a parent education intervention to increase parental monitoring in Hispanic parents of middle school children.^ The first study described the process of intervention mapping as used to develop Padres Trabajando por la Paz, a newsletter intervention for parents. Using theory, empirical literature, and information from the target population, performance objectives and determinants for monitoring were defined. Learning objectives were specified and a staged social-cognitive approach was used to develop methods and strategies delivered through newsletters.^ The second study examined the outcomes of a randomized trial of the newsletter intervention. Outcome measures consisted of a general measure of monitoring, parent and child reports of monitoring behaviors targeted by the intervention, and psychosocial determinants of monitoring (self-efficacy, norms, outcome expectancies, knowledge, and beliefs). Seventy-seven parents completed the randomized trial, half of which received four newsletters over an eight-week period. Results revealed a significant interaction effect for baseline and treatment for parent's reports of norms for monitoring (p =.009). Parents in the experimental condition who scored low at baseline reported increased norms for monitoring at follow-up. A significant interaction effect for child reports of parental monitoring behaviors (p =.04) reflected an small increase across baseline levels in the experimental condition and decreases for the control condition at higher baseline scores. Both groups of parents reported increased levels of monitoring at follow-up. No other outcome measures varied significantly by condition.^ The third study examined the relationship between the psychosocial determinants of parental monitoring and parental monitoring behaviors in the study population. Weak evidence for a relationship between outcome expectancies and parental monitoring behaviors suggests further research in the area utilizing stronger empirical models such as longitudinal design and structural equation modeling.^ The low-cost, minimal newsletter intervention showed promise for changing norms among Hispanic parents for parental monitoring. In light of the importance of parental monitoring as a protective factor for youth health risk behaviors, more research needs to be done to develop and evaluate interventions to increase parental monitoring. ^